EPSTEIN-BARR-VIRUS INFECTION IS AN EARLY EVENT IN GASTRIC CARCINOGENESIS AND IS INDEPENDENT OF BCL-2 EXPRESSION AND P53 ACCUMULATION

Ninety-five cases of adenocarcinoma of the stomach were evaluated for the presence of Epstein-Barr virus (EBV) using a sensitive in situ hyb ridization assay targeting Epstein-Barr virus-encoded RNA 1 (EBER1) tr anscripts. EBER1 was detected in 11 of 95 (12%) of cases. When present , the virus was localized to malignant epithelial cells and to dysplas tic gastric epithelium, but was not seen in normal-appearing gastric e pithelium or intestinal metaplasia. The EBV DNA was monoclonal in all three cases tested by Southern blot analysis of the EBV terminal repea t fragment. These findings suggest that the virus was present before m alignant transformation. The presence of EBV was strongly associated w ith increased numbers of tumorinfiltrating T lymphocytes; however, EBV was not associated with prolonged survival. Neither p53 nor bcl-2 wer e consistently detected in the EBV-associated tumors. Specifically, 6 of Ii EBV-positive carcinomas had accumulation of p53 protein by immun ohistochemical analysis, which was similar to the prevalence of p53 ac cumulation in EBV-negative specimens and suggests that EBV infection d oes not substitute for p53 mutation during tumorigenesis. The bcl-2 on coprotein was expressed in a third of the carcinoma specimens tested, but bcl-2 expression did not correlate with the presence of EBV or wit h expression of EBV latent membrane protein 1. In conclusion, EBV infe ction appears to precede malignant transformation in a significant fra ction of gastric carcinomas, but neither bcl-2 expression nor p53 accu mulation appear to be consistently associated with the presence of the virus.